This invention is concerned with viruses such as the vaccinia and fowlpox viruses modified to contain the DNA sequence (gene) which will express in a mammalian host, including humans, a protein corresponding to the conserved, exposed region of the M6 protein. It is concerned also with the use of such modified products as vaccines to protect against streptococcal infection. Further, it is concerned with plasmids or other vectors carrying the said gene.
Approximately 30 million cases of group A streptococcal infections occur each year in the United States, the most common of which is acute streptococcal pharyngitis which is found predominantly in school age children. Up to 5% of pharyngitis cases which have gone untreated, or have been ineffectively treated, can lead to acute rheumatic fever, a disease which can ultimately result in cardiac damage. While not a major problem in the United States, this streptococcal sequelae is a significant problem in developing nations of the world. For example, it has been estimated that nearly 6 million children of school age in India suffer from rheumatic heart disease.
The M protein of group A streptococci is a fibrous dimer of helices arranged in a coiled coil extending about 50 nm from the surface of these organisms. It is a fibrillar molecule of which there exists more than 80 serological types M. The protein renders the streptococcus resistant to nonimmune phagocytosis. It is the major virulence factor of streptococcal bacteria.
Thus, there are over 80 distinct serotypes of group A streptococci such that a vaccine based on type-specific epitopes may not be practical. In general, no satisfactory vaccine which will confer protection against streptococcal infection has yet been developed, although significant and costly efforts have been directed towards that end.
There is a strong impetus to develop a safe and effective vaccine against group A streptococci.